The present invention relates to a series of new peptides which have the ability to inhibit the activity of protease originating in the human immunodeficiency virus ("HIV"), hereinafter referred to as "HIV protease". The compounds thus have the ability to interfere with the maturation and replication of the virus and so may be used to treat individuals infected with HIV. The invention also provides methods and compositions using these compounds as well as processes for preparing them.
The pol genetic region of HIV contains genetic information relating to the activities of protease, reverse transcriptase, RNase H and endonuclease, and it is known that these enzymes are essential for the maturation of HIV particles and that HIV with infectious activity can never mature if the virus is deficient in any one of these enzyme activities (Science, December 1988).
Accordingly, attempts have been made to develop compounds capable of inhibiting these enzymes. For example, several compounds, including pepstatin A, are known to have this class of activity. Examples of such compounds are disclosed in Japanese Patent Kokai Application No. Hei 2-42048 (European Patent Publication No. 346 847); Japanese Patent Kokai Application No. Hei 2-117615 (European Patent Publication No. 357 332); Japanese Patent Kokai Application No. Hei 2-145515 (European Patent Publication No. 369 141); Japanese Patent Kokai Application No. Hei 2-152949 (European Patent Publication No. 356 223); Japanese Patent Kokai Application No. Hei 2-202898 (European Patent Publication No. 372 537); Japanese Patent Kokai Application No. Hei 2-202899 (European Patent Publication No. 373 497); Japanese Patent Kokai Application No. Hei 2-209854 (European Patent Publication No. 337 714); Proceedings of the National Academy of the United States of America 85, 6612 (1988); Biochemical and Biophysical Research Communications 159, 420 (1988); Biochemistry 29, 264 (1990); Proceedings of the National Academy of the United States of America 86, 9752 (1989); Nature 343, 90 (1990); Science 246, 1149 (1989); Science 247, 454 (1990); Science 248, 358 (1990); Science 249, 527 (1990); and Journal of Medicinal Chemistry 33, 1285 (1990)].
The prior art compounds, however, have a different structure from the compounds of the present invention.